Two synthetic peptides for treatment and prevention of cancers

ABSTRACT

Two synthetic peptides, Atroporin (AT) and Kaotree (KT), each consisting of ten amino acids and their use for the treatment and/or prevention of various types of cancers is disclosed. The amino acid sequence from the N-terminal for AT is Phe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg, and for KT is Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser.

TECHNICAL FIELD

[0001] In one aspect, the invention relates to synthetic peptides. Inanother aspect, the invention relates to the use of synthetic peptidesin the prevention of, and/or treatment of, cancers in humans.

BACKGROUND OF THE INVENTION

[0002] Currently, numerous chemicals are being used to treat varioustypes of cancers and such treatment is termed as chemotherapy.Chemotherapy is associated with adverse side effects, such as hair loss,diarrhea, skin rash etc. simply because the chemicals used to killcancer cells also affect normal cells adversely. Chemotherapy requiresdifferent chemical drugs to treat different types of cancers.

[0003] In our U.S. Pat. No. 5,565,431, the disclosure of which isincorporated herein by reference, cancer cell inhibitors Atroporin (AT)and Kaotree (KT) were isolated by fractionating venoms of Crotalus atroxand Naja kaouthia snakes respectively by high pressure liquidchromatography (HPLC). Atroporin (AT) had a molecular weight ofapproximately 35,000 Daltons, whereas Kaotree (KT) had a molecularweight of approximately 6,000 Daltons. The homogeneous preparation of ATand KT showed killing effects on several types of human (breast, colon,liver, ovary etc.) and animal cancer cells in concentration as low as0.5 μg/ml, and having no effect on normal mouse kidney, liver and spleencells as high as 5.0 μg/ml. Both Atroporin and Kaotree exhibited theproperty of preventing the formation and regression of ascitic tumorscaused by myeloma cells in Balb/c mice. The combination of AT and KTshowed elevated anticancer activity in both in vitro and in vivosystems.

[0004] The relatively large molecular sizes of intact AT and KT limitthe routes by which they can be administered.

[0005] The relatively large molecular sizes of AT and KT also raises thepossibility of patient adverse reactions.

[0006] The fact that AT and KT are derived from venoms further makesgaining commercial acceptance more difficult.

[0007] Smaller molecules which mimic the properties of AT and KT and arenot derived from venom would be very desirable.

OBJECTS OF THE INVENTION

[0008] It is an object of this invention to claim synthetic (Syn)peptides based on active fragments of AT and KT and their use to treatand prevent various types of cancer. Syn AT and Syn KT individually orin combination show cytolytic activity to a wide range of tumor cells,in both in vitro and in vivo systems. A further object of this inventionis to provide a non toxic cancer treatment without a typical adverseeffect caused by usual chemotherapy because AT and KT having selectivelykilling effects on cancer cells leaving normal cells unaffected.Furthermore, the combination of AT and KT exhibits enhanced cytolyticactivity for certain types of cancer. Hence, it is a further object ofthe invention to claim that the combination may lead to more effectivecancer therapy. The treatment in liquid form can be given by buccalroute under the tongue, or by injections. The bioavailability of suchsmall molecules having low molecular weight will get into thecirculation immediately like chemical drugs without getting degraded.

SUMMARY OF THE INVENTION

[0009] In one embodiment of the invention, we provide a synthetic AT,which we broadly characterize as a peptide comprising at least the firstfive amino acids from the N-terminal of the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu and no more than 25amino acids total.

[0010] In another embodiment of the invention, we provide a syntheticKT, which we broadly characterize as peptide comprising at least thefirst five amino acids from the N-terminal of the sequencePro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn and no more than 25 aminoacids total.

[0011] In a further embodiment of the invention, we provide a cancertreatment method, which we broadly characterize as administering acytolytically effective amount of a cytolytic agent comprising at leastone of the above peptides to a cancer patient in a manner to reach thebloodstream of the patient.

[0012] In another embodiment, we provide a method for preventingsymptomatic cancer in a patient susceptible to same by administering tosaid patient preventative amount of a cytolytic agent comprising atleast one of the above peptides.

DETAILED DESCRIPTION OF THE INVENTION

[0013] Cancer cell inhibitors Atroporin (AT) and Kaotree (KT) wereisolated by fractionating Crotalus atrox and Naja kaouthia snake venomsrespectively by high pressure liquid chromatography. The presentinvention relates to the identification of the active domains/fragmentsof the natural AT and KT, which mimic the cytolytic activity of theparent molecules against cancer cells in vitro and in animals, and theproduction of synthetic peptides which mimic the cytolytic activity ofthe fragments.

[0014] The most active fragment for AT consisted of 13 of amino acidsand had the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu. (SEQ. ID. NO.: 1)

[0015] The most active fragment for KT consisted of 11 amino acids andhad the sequence Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn. (SEQ. ID.NO.: 2)

[0016] Two synthetic constructs, consisting of ten and five amino acids,were made based on portions of these fragments.

[0017] The two synthetic constructs for AT, from N-terminal, were:

[0018] SEQ. ID. NO. 3: Phe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg

[0019] consisting of 10 amino acids, and

[0020] SEQ. ID. NO. 4: Phe-Cys-Arg-Phe-Leu

[0021] consisting of five amino acids.

[0022] The two synthetic constructs for KT, from the N-terminal, were:

[0023] SEQ. ID. NO. 5: Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser

[0024] consisting of 10 amino acids, and.

[0025] SEQ. ID. NO. 6: Pro-Pro-Gly-Asn-Gln

[0026] consisting of five amino acids.

[0027] In tests, the synthetic 10 amino acid peptides proved mostactive, and the invention relates primarily to these synthetic versionsof AT and KT, each consisting of ten amino acids, which are inhibitoryto cancer cells. Syn. AT and KT individually or in combinationselectively kill various types of cancer cells when tested in cellcultures.

[0028] In mice the treatment with AT or KT prolong the incubationperiods for the formation of ascitic tumors caused by SP/2 cancer cellsin comparison to the controls, for death. The combination of AT and KTtreatment caused 50% survival in mice in comparison to the untreatedcontrols. Based upon these results, the combination of syn. AT and KT ispreferably proposed to treat various types of cancers in humansincluding Kaposi sarcoma in AIDS patients.

[0029] Conversion of AT and KT to Synthetic Versions:

[0030] We realized that natural products specially coming from snakevenoms will have resistance from FDA. Furthermore, production willdepend on the availability of venoms. By our proprietary technology andpains taking research, anti-cancer active domains for natural AT and KTwere identified. Synthetic peptides consisting of ten amino acids foreach were made using well known automated procedures and were designatedas syn AT and syn KT.

[0031] Purification of AT and KT from Snake Venoms:

[0032] The homogeneous preparations of natural AT and KT were obtainedby fractionating venoms of C. atrox and N. kaouthia on HPLC using ionexchange column and gradient Trizma buffer pH 7.4 (U.S. Pat. No.5,565,431 1996; entitled, “Cancer Cell Inhibitors and Method”).

[0033] Trypsin Digestion of Natural AT and KT:

[0034] Purified homogeneous preparations of AT and KT were treated withtrypsin dissolved in 0.1 M ammonium bicarbonate buffer pH 8.0. The ATand KT proteins individually were mixed with trypsin in 40:1 ratio.Precisely 5 mg of AT or KT was mixed with 0.125 mg of trypsin. Themixtures were incubated at 37° C. to cause fragmentation at arginine andlysine sites. After 18 hours of incubation the reaction was stopped bycooling the mixtures at 4° C.

[0035] Separation of Trypsin Digested Fragments:

[0036] The fragments of AT and KT digested with trypsin were separatedon HPLC. The fragments for AT and KT were collected individually anddialyzed against water using 500-Dalton molecular weight cutoff tubing(Spectrum Co. USA). The protein concentration of each fragment wasmeasured by spectrophotometer using a protein kit from Bio-Rad Co.(USA). Each fragment was adjusted in concentration to 100 μg/ml with0.05 M phosphate buffered saline (PBS). The fragments of trypsindigested AT and KT were separated on HPLC. HPLC separation resolved ATresolves into 7 fragments and KT 13 fragments.

[0037] Biological Activity of Fragments on SP/2 Cells:

[0038] The cytolytic activity of the trypsin digested fragments of ATand KT were tested on 10⁵ SP/2 cells. Dulbecco Modified Eagle's Medium(DMEM) containing 10% newborn calf serum (NBCS), L-glutamine andantibiotics penicillin and streptomycin was used to grow SP/2 cells.Initially, each fraction was tested on cells grown in 48 well plate at37° C. in a humid CO2 incubator. The serum free medium containingdifferent concentrations such as 20, 10, 5, 2.5 and 1.0 μg/ml of eachfragment was tested. Control cells received PBS to serve as controls.

[0039] Identification of Active Fragment:

[0040] The tests were read after three days. It was revealed that one ofthe fragments for each AT and KT showed the highest cytolytic activityon SP/2 cells. Those fragments were considered as the active domains forcancer cell inhibitor. The fragment 6 for AT and 10 for KT were found tobe the most active for cytolytic activity when tested on SP/2 cells. Thefragment 6 for AT and the fragment 10 for KT were considered as theactive domains for cytolytic activity. The most active fragments 6 forAT and 10 for KT were sequenced for their amino acids composition. Thesequence for the most active fragment from N-terminal for AT consistingof 13 amino acids was found to bePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu. The sequence forthe most active fragment from N-terminal for KT consisting of 11 aminoacids was found to be Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn.

[0041] Conversion of Active Domain to Synthetic Peptides:

[0042] Two synthetic constructs, consisting of ten and five amino acidsfor each, were made from the most active fragment of AT and KT.

[0043] The two synthetic constructs for AT from N-terminal of SEQ ID.NO. 1 were:

[0044] SEQ. ID. NO. 3, Phe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg

[0045] consisting of 10 amino acids, and

[0046] SEQ. ID. NO. 4, Phe-Cys-Arg-Phe-Leu

[0047] consisting of five amino acids.

[0048] The two synthetic constructs for KT from N-terminal of SEQ ID.NO. 2 were:

[0049] SEQ. ID. NO. 5, Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser

[0050] consisting of 10 amino acids, and

[0051] SEQ. ID. NO. 6, Pro-Pro-Gly-Asn-Gln

[0052] consisting of five amino acids.

[0053] In vitro Biological Activity of syn AT and syn KT:

[0054] Biological cytolytic activity of AT and KT at variousconcentrations ranging from 3.5, 6.25, 12.5 and 25 μg/ml were tested onhuman cancer cells and SP/2 mouse myeloma cells. The results were readmicroscopically the results are shown in Table 1. The combination AT+KTwas 50% by weight of each. TABLE 1 Cytolytic effect of syn AT and syn KTindividually and in combination on cancer cells. % Cytolyic cells HBL-Agent μg/ml 100 BT-20 HT-29 Sk-ov-3 CCL-13 SP/2 Atroporin 25 100 100 100100 100 100 12.5 50 50 100 100 100 50 6.25 0 0 0 100 50 0 3.12 0 0 0 0 00 Kaotree 25 100 100 100 100 100 100 12.5 100 75 100 100 100 100 6.25 500 0 50 0 50 3.12 0 0 0 0 0 0 Atroporin + 25 100 100 100 100 100 100Kaotree 12.5 100 100 100 100 100 100 6.25 100 0 50 100 50 50 3.12 0 0 00 0 0

[0055] Results of table 1 show the killing effect of syn. AT and syn KTindividually on cancer cells at varying concentrations. The results showthat syn. KT is more cytolytic than AT in similar concentration forHBL-100, BT-20, breast cancer cells. AT is more cytolytic to Sk-ov-3ovarian cancer cells than AT in similar concentration. However,combination of AT and KT is more cytolytic than the individual.

[0056] Anti Cancer Activity of Synthetic AT and KT In Vivo:

[0057] Adult Balb/c mice were injected intra-peritoneally with 0.5 mlcontaining 2 million SP/2 cancer cells. Mice were divided into fourgroups. Starting from day one of post injection the mice were treatedwith AT and KT individually and the combination of both at 200 μg/mlconcentration. Doses of 0.5 ml containing 100 μg/mouse were given forseven consecutive days and the control mice received 0.5 ml PBS. Resultsare shown in table 2. TABLE 2 Treatment versus Incubation period forsurvival in days Group Treatment Survival I PBS 23 days II Syn AT 30days III SYN KT 37 days IV Both AT & KT 50% at 60 days

[0058] Results show that the treatment with syn. AT and KT individuallyprolonged the incubation period for the development of ascitic tumors tocause death, 30 and 37 days versus 23 days for untreated or injectedwith PBS. Combination of syn-AT and KT yielded 50% survival. It isnoteworthy that the treatment period continued for only 7 days.

[0059] In vitro combination of AT and KT provides enhanced killingeffect on various types of cancer cells. In vivo combination of AT andKT prolongs incubation period to form tumors and showed 50% survival,therefore the combination of syn AT and KT is preferably proposed forhuman therapy. For such use, the composition will generally contain,based on weight, in the range of 10% to 90% of AT, balance KT, usuallyin the range of 30% to 70% AT, balance KT.

[0060] Based on a 50 kilogram human having approximately 2500 times themass of a 20 gram mouse, an equivalent dose of peptide(s) (alone orcombined) for humans as was tested on mice is believed on the order of250 milligrams/day. For treating cancer in humans, a dosage level in therange of about 5 milligrams to 5,000 milligrams daily is believedbroadly suitable, depending on the size of the patient, the severity andtype of cancer, and the period of treatment. It is expected that thedosage will generally be in the range of 100 to 1,000 milligrams per dayand continue for a period of time in the range of 1 to 100 days,generally in the range of 5 to 50 days. Because the peptides are of lowmolecular weight, they can be orally or bucally administered if desired,although intravenous administration will also be suitable.

[0061] Prevention of Cancer:

[0062] We propose the combination of synthetic versions of cancer cellinhibitors AT and KT as an effective, and, most importantly, non-toxictreatment for prevention of cancer.

[0063] In the prosperous countries, roughly 20%, or one in five will dieof cancer. The most frequently occurring cancers worldwide in descendingorder are: stomach, lung, breast, colon/rectum, cervix andmouth/pharynx. Surgery, chemotherapy and radiation show limited success,but these procedures remove or destroy normal cells along with cancercells. The search for treatments for cancer has been vigorously pursuedfor over a half century, and the use of chemicals to treat cancercontinues. The treatment of cancer needs to be changed from chemotherapyto biotherapy using small biological peptides having minimal, or noadverse effects.

[0064] To date, there is no preventive therapy for cancer. We stronglybelieve that the syn AT and KT, being capable of killing selectivelycancer cells, should fill this gap. Population of people havingpredisposition for cancer, due to hereditary or other reasons should begiven this treatment, may be once or twice a year. AT and KT willfunction like vaccine for prevention of cancer, although their activityis not due to the antibodies production but due to selective killingeffect. Of course, the necessary controlled studies will require longperiod of time and a lot of investment.

[0065] For this application, it is expected that a dosage level in therange of 5 milligrams to 250 milligrams per day continuing for a periodof time in the range of 1 to 10 days will be suitable, to be repeatedevery few months.

[0066] Treatment or Prevention of Recurrence for Cancer:

[0067] During a normal healthy life cancer cells are constantly formeddue to mutation and are removed at the same rate by the natural killercells. If, for whatever reason, the cancer cell number overrides thenatural killer cell population, the cancer cells become established inbody organs. A tumor is an aggregation of cancer cells due to excessiverapid growth property of cancer cells. By the time the patient isdiagnosed for cancer, the cancer may be metastasized. Diagnosisgenerally leads to surgery to remove cancer growth or tumor, followed bychemotherapy. Even after surgery most of the times the cancer comesback.

[0068] Syn. peptides AT and KT are non toxic to normal cells theirkilling effect is selectively for various types of cancer cells.Combination of syn. AT and KT treatment can cause regression of tumors,depending upon the size of the cancer tumor. In such case where surgeryis inevitable the combination of AT and KT can serve as a treatment toprevent recurrence of cancer.

[0069] Further Details

[0070] The syn AT peptide contains at least the first five amino acidsfrom the N-terminal of the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu somewhere in itsbackbone and no more than 25 amino acids total. Preferably, the syn ATpeptide contains no more than 20 amino acids, and more preferably nomore than 15 amino acids, because smaller peptides are less expensive tosynthesize. On the other hand, the syn AT which showed the greatestpromise had 10 amino acids, so it is most preferred that the syn ATpeptide consists of at least the first 10 amino acids of the statedsequence.

[0071] The syn KT peptide contains at least the first five amino acidsfrom the N-terminal of the sequencePro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn somewhere in its backboneand no more than 25 amino acids total. Preferably, the syn KT peptidecontains no more than than 20 amino acids, and more preferably no morethan 15 amino acids, because smaller peptides are less expensive tosynthesize. On the other hand, the syn KT which showed the greatestpromise had 10 amino acids, so the most preferred syn KT consists of atleast the first 10 amino acids of the sequence.

[0072] The syn AT and syn KT peptides, alone or together, constitutecytolytic agents and thus may be used to treat a human cancer patient byadministering an effective amount thereof to the patient in a manner toreach the bloodstream. Because the peptides are small, a variety ofadministration techniques can be used, including nasal insufflation,buccal administration, oral ingestion, intravenous injection andintramuscular injection. It is expected generally that in the range of 5milligrams to 5,000 milligrams of the cytolytic agent will beadministered daily over a period of time in the range of 1 to 100 days,and that the cancers will generally be from the group stomach cancer,lung cancer, breast cancer, colon/rectum cancer, cervical cancer,mouth/pharynx cancer, and Kaposi sarcoma. Utilizing both of the peptidestogether would be preferred. For the prevention of these cancers insusceptible populations, it is expected in the range of 5 milligrams to250 milligrams would be administered daily for a period of time in therange of 1 to 10 days.

[0073] While certain preferred embodiments of the invention have beendescribed herein, the invention is not to be construed as being solimited, except to the extent that such limitations are found in theclaims.

1 6 1 13 PRT Artificial Sequence Fragment of 35,000 Dalton Proteinisolated from Crotalus atrox venom (See US 5,665,431) 1 Phe Cys Arg PheLeu Leu Cys Pro Ser Arg Ser Leu Leu 1 5 10 2 11 PRT Artificial SequenceFragment from 6,000 Dalton Protein Isolated from Naja Kaouthia Venom(see US 5,665,431) 2 Pro Pro Gly Asn Gln Pro Asp Ala Asp Ser Asn 1 5 103 10 PRT Artificial Sequence Synthetic. Fragment of SEQ ID NO 1 3 PheCys Arg Phe Leu Leu Cys Pro Ser Arg 1 5 10 4 5 PRT Artificial SequenceSynthetic. Fragment of SEQ ID NO 3 4 Phe Cys Arg Phe Leu 1 5 5 10 PRTArtificial Sequence Synthetic. Fragment of SEQ ID NO 2 5 Pro Pro Gly AsnGln Pro Asp Ala Asp Ser 1 5 10 6 5 PRT Artificial Sequence Synthetic.Fragment of SEQ ID NO 5 6 Pro Pro Gly Asn Gln 1 5

What is claimed is:
 1. Composition of matter comprising AT and KT aresynthetic peptides each consisting of ten amino acids. Syn AT havingamino acids sequence from N-terminalPhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg and for KTPro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser.
 2. The syn peptides AT and KTmimic the biological properties of the intact natural AT and KT,particularly in regards to causing cytolysis of various types of cancercells and prolongation of incubation period for the death in mice. 3.The combination of AT and KT treatment yielded 50% survival of miceinjected with myeloma cancer cells versus 100% death in control mice.Therefore, the combination of syn AT and KT has potential for treatingvarious types of cancers.
 4. Syn. AT and KT can be made in abundancewithout depending on snake venoms. The combination treatment can begiven by injections or orally by buccal cavity.
 5. A composition ofmatter comprising a peptide comprising at least the first five aminoacids from the N-terminal of the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu and no more than 25amino acids total.
 6. A composition of matter as in claim 5 wherein thepeptide contains no more than 20 amino acids.
 7. A composition of matteras in claim 5 wherein the peptide contains no more than 15 amino acids.8. A composition of matter as in claim 5 wherein the peptide consists ofat least the first 10 amino acids of the sequence.
 9. A composition ofmatter comprising a peptide comprising at least the first five aminoacids from the N-terminal of the sequencePro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn and no more than 25 aminoacids total.
 10. A composition of matter as in claim 9 wherein thepeptide contains no more than 20 amino acids.
 11. A composition ofmatter as in claim 9 wherein the peptide contains no more than 15 aminoacids.
 12. A composition of matter as in claim 9 wherein the peptideconsists of at least the first 10 amino acids of the sequence.
 13. Amethod for treating a human cancer patient comprising administering aneffective amount of a cytolytic agent to said patient in a manner toreach the bloodstream of the patient, said cytolytic agent comprising apeptide comprising at least the first five amino acids from theN-terminal of the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu and no more than 25amino acids total.
 14. A method as in claim 13 wherein the patient is avictim of a cancer selected from the group consisting of stomach cancer,lung cancer, breast cancer, colon/rectum cancer, cervical cancer,mouth/pharynx cancer, and Kaposi sarcoma, the administration techniqueis selected from the group consisting of nasal insufflation, buccaladministration, oral ingestion, intravenous injection and intramuscularinjection, and the cytolytic agent contains a 10 amino acid peptidehaving the sequence Phe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg.
 15. Amethod as in claim 13 wherein 5 milligrams to 5,000 milligrams of thecytolytic agent are administered daily over a period of time in therange of 1 to 100 days.
 16. A method for treating a human cancer patientcomprising administering an effective amount of a cytolytic agent tosaid patient in a manner to reach the bloodstream of the patient, saidcytolytic agent comprising a peptide comprising at least the first fiveamino acids from the N-terminal of the sequencePro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn and no more than 25 aminoacids total.
 17. A method as in claim 16 wherein the patient is a victimof a cancer selected from the group consisting of stomach cancer, lungcancer, breast cancer, colon/rectum cancer, cervical cancer,mouth/pharynx cancer, and Kaposi sarcoma, the administration techniqueis selected from the group consisting of nasal insufflation, buccaladministration, oral ingestion, intravenous injection and intramuscularinjection, and the cytolytic agent contains a 10 amino acid peptidehaving the sequence Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser.
 18. Amethod as in claim 16 wherein 5 milligrams to 5,000 milligrams of thecytolytic agent are administered daily over a period of time in therange of 1 to 100 days.
 19. A method for treating a human cancer patientcomprising administering an effective amount of a cytolytic agent tosaid patient in a manner to reach the bloodstream of the patient, saidcytolytic agent comprising a first peptide comprising at least the firstfive amino acids from the N-terminal of the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu and no more than 25amino acids total, and a second peptide comprising at least the firstfive amino acids from the N-terminal of the sequencePro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn and no more than 25 aminoacids total.
 20. A method as in claim 19 wherein the cytolytic agentcomprises a 10 amino acid first peptide having the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg, and a 10 amino acid secondpeptide having the sequence Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser. 21.A method as in claim 19 wherein the patient is a victim of a cancerselected from the group consisting of stomach cancer, lung cancer,breast cancer, colon/rectum cancer, cervical cancer, mouth/pharynxcancer, and Kaposi sarcoma, and the administration technique is selectedfrom the group consisting of nasal insufflation, buccal administration,oral ingestion, intravenous injection and intramuscular injection.
 22. Amethod as in claim 19 wherein 5 milligrams to 5,000 milligrams of thecytolytic agent are administered daily over a period of time in therange of 1 to 100 days.
 23. A method for preventing symptomatic cancerin a human comprising administering to said patient an preventativeamount of a cytolytic agent to said patient in a manner to reach thebloodstream of the patient, said cytolytic agent comprising at least oneof a first peptide comprising at least the first five amino acids fromthe N-terminal of the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg-Ser-Leu-Leu and no more than 25amino acids total, and a second peptide comprising at least the firstfive amino acids from the N-terminal of the sequencePro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser-Asn and no more than 25 aminoacids total
 24. A method as in claim 23 wherein the cytolytic agentcomprises both of the peptides.
 25. A method as in claim 24 where thecytolytic agent comprises a 10 amino acid peptide having the sequencePhe-Cys-Arg-Phe-Leu-Leu-Cys-Pro-Ser-Arg, and a 10 amino acid peptidehaving the sequence Pro-Pro-Gly-Asn-Gln-Pro-Asp-Ala-Asp-Ser
 26. A methodas in claim 23 wherein in the range of 5 milligrams to 250 milligramsare administered daily for a period of time in the range of 1 to 10days.